美国埃默里大学Winship癌症中心Sagar Lonial教授访谈

　　《肿瘤瞭望》：尽管FDA批准帕比司他用于MM的治疗，但其毒副作用严重，您怎样看待这一问题？

　　Lonial教授：我认为应用帕比司他时对不良反应的管理、以及帕比司他的给药剂量和给药时间都十分重要。帕比司他与其他药物的联合治疗时，已不再静脉应用硼替佐米，因为皮下应用硼替佐米或口服卡非佐米联合帕比司他（相比于静脉应用硼替佐米）的毒性作用更小。如果给药时间调整为隔周给药，其毒性反应还可以降至更低。因此，该药的给药剂量和时间的选择发挥了关键的作用。

　　I think that the adverse effect management of panobinostat is really important， and I think dose and scheduleare really important. I also think the partner drug for combining with panobinotsat is really important. We don’t use intravenous bortezomib at all anymore. When you use subcutaneous bortezomib， or even now， when you use carfilzomib in combination with panobinostat， the toxicity is much less， and if you give a one week on-one week off-one week on schedule， the toxicity seems to drop pretty markedly as well. So I think it is dose and schedule.

　　《肿瘤瞭望》：您提到目前有一些新药如darbtumumab可以用于多发性骨髓瘤的治疗。您认为在这一背景下，帕比司他未来前景如何？

　　Lonial教授：我认为有更多的新药投入使用是令人兴奋的事，darbtumumab是免疫调节治疗的一个关键药物。但是，我认为骨髓瘤的治疗策略应该是联合用药。因此，不论使用何种新药，我们都强调联合用药。理想的状态是，在适合的患者中，应用帕比司他、蛋白酶体抑制剂以及免疫调节剂联合治疗。

　　目前帕比司他用于其它血液病的数据多为早期试验数据。据了解，目前帕比司他应用于霍奇金淋巴瘤的临床试验正在进行当中，尚未得出相关的应用数据。此外，人们还尝试在白血病和骨髓增生异常综合征中应用帕比司他。

　　I think that certainly having more new drugs is really exciting for us， and darbtumumab gives us the opportunity for immune-based therapies. But I think that the world of myeloma therapy is combinations. So， no matter what we do we are going to have combinations. Panobinostat can combine with proteasome inhibitors and with amides， and I think in the right patient population that is the combination you want to use. I know that they’ve tried looking at Hodgkin lymphoma and the data didn’t end up panning out in that clinical situation. There are other trials， I think， looking at leukemia and myelodysplastic syndrome

　　《肿瘤瞭望》：请问目前有哪些生物学标志物可以预测帕比司他的效果？

　　Lonial教授：生物学标志物的确十分重要，它可使帕比司他的临床应用变得更容易。但是，目前我们还没有找到相应的生物学标志物。如果患者的蛋白负荷高、内质网应激反应强烈，那么他们对帕比司他也许更加敏感，但是我们还没有发现一种生物学标志物可以预测其效果。如果患者有条件可以使用昂贵些的药物，帕比司他是选择之一，它与卡非佐米以及来那度胺三药联合治疗MM疗效令人期待。

　　The biomarker story is really important because it would make it so much easier for us. I don’t think we know that there’s a biomarker right now. Patients that have more protein load and more ER stress may be more sensitive， but we don’t have a biomarker for that. If you need a little expensive to combine， I would really consider using it in combination with carfilzomiband now， with lenalidomide. It’s a very interesting combination，lenalidomide and carfilzombib.